Association Between REELIN Gene Polymorphisms (rs7341475 and rs262355) and Risk of Schizophrenia: an Updated Meta-analysis

Schizophrenia (SCZ) is a destructive neuropsychiatric illness affecting millions of people worldwide. The correlation between RELN gene polymorphisms and SCZ was investigated by previous researches, though the results remained conflicting. Based on the available studies, we conducted this meta-analysis to provide a more comprehensive outcome on whether the RELN gene polymorphisms (rs7341475 and rs262355) are associated with SCZ. A total of 15 studies with 25,403 subjects (9047 cases and 16,356 controls) retrieved from PubMed, ScienceDirect, EMBASE, Wiley, BMC, Cochrane, Springer, MDPI, SAGE, and Google Scholar up to June 2020 were included. Meta-analysis was performed using Review Manager 5.3. The heterogeneity was checked using I² statistics and Q-test, whereas publication bias was also measured. The rs7341475 polymorphism showed a significantly lower risk for SCZ for the allele (A vs. G: OR = 0.93, 95%CI = 0.87-0.99), codominant 1 (AG vs. GG: OR = 0.92, 95%CI = 0.85-0.99), dominant model (AA+AG vs. GG: OR = 0.92, 95%CI = 0.86-0.98), and over dominant model (AG vs. AA+GG: OR = 0.92, 95%Cl = 0.86-0.99). The allele, codominant model 1, and dominant models remained statistically significant after the correction of the Bonferroni (p < 0.025). Subgroup analysis confirmed the association of allele and dominant models in the Caucasian after Bonferroni correction. For rs262355 polymorphism, a significantly increased risk of SCZ was found only in Caucasians for codominant 2, dominant, and allele models, but significance exists only for the allele model after Bonferroni correction. Publication bias was found in the case of codominant 2 and recessive models for rs7341475 in the overall population, but this publication was not found after performing the Bonferroni correction or after performing the subgroup analysis. No such publication was found for rs262355. The results suggest that RELN rs7341475 is associated with a lower risk of SCZ in the overall population and Caucasian population, but rs262355 is associated with an increased risk of SCZ only in the Caucasian population.